bosmolisib

BR101801 (bosmolisib) is an orally administered, small molecule inhibitor that targets phosphoinositide 3-kinase gamma and delta isoforms (PI3Kγ/δ) as well as DNA-dependent protein kinase (DNA-PK). By inhibiting PI3Kγ/δ, it disrupts signaling pathways involved in cell growth and survival. Inhibition of DNA-PK impairs the non-homologous end joining (NHEJ) pathway for DNA double-strand break repair, leading to increased genomic instability and apoptosis in cancer cells. This triple inhibition also decreases the stability of oncogenic proteins such as c-Myc. Preclinical studies have shown that BR101801 can induce cell cycle arrest, promote autophagic cell death, enhance antitumor immune responses—especially when combined with irradiation—and sensitize tumors to radiotherapy by impairing both NHEJ and homologous recombination repair mechanisms. It has demonstrated antitumor activity in hematologic malignancies such as relapsed/refractory peripheral T-cell lymphoma (PTCL), diffuse large B-cell lymphoma (DLBCL), angioimmunoblastic T-cell lymphoma (AITL), marginal zone lymphoma (MZL), mycosis fungoides (MF), and solid tumors[1][4][5][6][7][8].

Other names

DNA-PK/PI3K-delta inhibitor BR101801